Multivariate approach for longitudinal analysis of brain metabolite levels from ages 5-11 years in children with perinatal HIV infection
Noëlle van Biljon,
Frances Robertson,
Martha Holmes,
Mark F Cotton,
Barbara Laughton,
Andre van der Kouwe,
Ernesta Meintjes,
Francesca Little
Affiliations
Noëlle van Biljon
Department of Statistical Sciences, University of Cape Town, Private Bag X3, Rhodes Gift, 7707 Cape Town, South Africa; Biomedical Engineering Research Centre, Division of Biomedical Engineering, Department of Human Biology, University of Cape Town, South Africa
Frances Robertson
Biomedical Engineering Research Centre, Division of Biomedical Engineering, Department of Human Biology, University of Cape Town, South Africa; Cape Universities Body Imaging Centre, Cape Town, South Africa; Neuroscience Institute, University of Cape Town, South Africa
Martha Holmes
Biomedical Engineering Research Centre, Division of Biomedical Engineering, Department of Human Biology, University of Cape Town, South Africa; Neuroscience Institute, University of Cape Town, South Africa
Mark F Cotton
FAMCRU, Department of Paediatrics and Child Health and Tygerberg Children's Hospital, Stellenbosch University, Cape Town, South Africa
Barbara Laughton
FAMCRU, Department of Paediatrics and Child Health and Tygerberg Children's Hospital, Stellenbosch University, Cape Town, South Africa
Andre van der Kouwe
Biomedical Engineering Research Centre, Division of Biomedical Engineering, Department of Human Biology, University of Cape Town, South Africa; Athinoula A. Martinos Center, Massachusetts General Hospital, Charlestown, MA, United States
Ernesta Meintjes
Biomedical Engineering Research Centre, Division of Biomedical Engineering, Department of Human Biology, University of Cape Town, South Africa; Cape Universities Body Imaging Centre, Cape Town, South Africa; Neuroscience Institute, University of Cape Town, South Africa
Francesca Little
Department of Statistical Sciences, University of Cape Town, Private Bag X3, Rhodes Gift, 7707 Cape Town, South Africa; Corresponding author.
Treatment guidelines recommend that children with perinatal HIV infection (PHIV) initiate antiretroviral therapy (ART) early in life and remain on it lifelong. As part of a longitudinal study examining the long-term consequences of PHIV and early ART on the developing brain, 89 PHIV children and a control group of 85 HIV uninfected children (HIV-) received neuroimaging at ages 5, 7, 9 and 11 years, including single voxel magnetic resonance spectroscopy (MRS) in three brain regions, namely the basal ganglia (BG), midfrontal gray matter (MFGM) and peritrigonal white matter (PWM). We analysed age-related changes in absolute metabolite concentrations using a multivariate approach traditionally applied to ecological data, the Correlated Response Model (CRM) and compared these to results obtained from a multilevel mixed effect modelling (MMEM) approach. Both approaches produce similar outcomes in relation to HIV status and age effects on longitudinal trajectories. Both methods found similar age-related increases in both PHIV and HIV- children in almost all metabolites across regions. We found significantly elevated GPC+PCh across regions (95% CI=[0.033; 0.105] in BG; 95% CI=[0.021; 0.099] in PWM; 95% CI=[0.059; 0.137] in MFGM) and elevated mI in MFGM (95% CI=[0.131; 0.407]) among children living with PHIV compared to HIV- children; additionally the CRM model also indicated elevated mI in BG (95% CI=[0.008; 0.248]). These findings suggest persistent inflammation across the brain in young children living with HIV despite early ART initiation.
